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Abstract：
Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs). Only a few cases of MSUD have been documented in Mainland China. In this report, 8 patients (4 females and 4 males) with MSUD from 8 unrelated Chinese Han families were diagnosed at the age of 6 days to 4 months. All the coding regions and exon/intron boundaries of BCKDHA, BCDKHB, DBT and DLD genes were analyzed by targeted NGS in the 8 MSUD pedigrees. Targeted NGS revealed 2 pedigrees with MSUD Ia, 5 pedigrees with Ib, 1 pedigree with MSUD II. Totally, 13 variants were detected, including 2 variants (p.Ala216Val and p.Gly281Arg) in BCKDHA gene, 10 variants (p.Gly95Ala, p.Ser171Pro, p.Phe175Leu, p.Arg183Trp, p.Lys222Thr, p.Arg285Ter, p.Arg111Ter, p.S184Pfs*46, p.Arg170Cys, p.I160Ffs*25) in BCKDHB gene, 1 variant (p.Arg431Ter) in DBT gene. In addition, 4 previously unidentified variants (p.Gly281Arg in BCKDHA gene, p.Ser171Pro, p.Gly95Ala and p.Lys222Thr in BCKDHB gene) were identified. NGS plus Sanger sequencing detection is effective and accurate for gene diagnosis. Computational structural modeling indicated that these novel variations probably affect structural stability and considered as likely pathogenic variants.
摘要：
枫糖浆尿病（MSUD）是一种罕见的常染色体隐性遗传疾病，会影响支链氨基酸（BCAA）的降解。在中国大陆仅记录了少数MSUD病例。在这份报告中,来自8个无关的中国汉族家庭的8名MSUD患者（4名女性和4名男性）在6天至4个月的年龄被诊断。BCKDHA的所有编码区和外显子/内含子边界，BCDKHB,在8个MSUD家系中通过靶向NGS分析DBT和DLD基因。靶向NGS显示2个MSUDIa家系，5家系与Ib，1个谱系与MSUDII。完全正确,检测到13个变异，包括2个变体（p。Ala216Val和p.Gly281Arg）在BCKDHA基因中，10个变体（p。Gly95Ala,p.Ser171Pro,p.Phe175Leu,p.Arg183Trp,p.Lys222Thr,p.Arg285Ter,p.Arg111Ter,p.S184Pfs*46,p.Arg170Cys,p.I160Ffs*25)在BCKDHB基因中，1个变体（p。Arg431Ter)在DBT基因中。此外,4个先前未识别的变体（p。Gly281Arg在BCKDHA基因中，p.Ser171Pro,鉴定了BCKDHB基因中的p.Gly95Ala和p.Lys222Thr)。NGS加Sanger测序检测对基因诊断有效、准确。计算结构模型表明，这些新的变化可能会影响结构稳定性，并被认为是可能的致病变体。
